DMM019000F3: Treatment with sulindac upregulates HIF2α and downregulates MIF in Hif1αΔIEC mice compared with Hif1αF/F mice. Q-PCR analysis for gene expression of Hif1α (A), ITF (B), Glut1 (C), Pgk1 (D), Vegfa (E), Hif2α (F), MIF (G) and the macrophage marker F4/80 (H). RNA was extracted from the mucosal scrapings, and lesions were harvested from the proximal colon of Hif1αΔIEC and Hif1αF/F mice that had been treated with sulindac (Sul) or the control (Con) diet. The q-PCR primers for Hif1α span exons 2 and 3. Gene expression was normalised to that of Rpl19. Error bars indicate s.e.m. Star (*) indicates P<0.05.

Mentions:
We observed a 19-fold reduction of Hif1α mRNA expression in Hif1αΔIEC mice compared with that of the control genotype (Fig. 3A). The generation of Hif1αΔIEC involves deletion of exon 2, which contains sequences encoding the basic helix-loop-helix (bHLH) domain that is essential for DNA binding and dimerisation of HIF1α and HIF1β (Jiang et al., 1996), and that results in downregulation of HIF1α-target genes (Iyer et al., 1998; Ryan et al., 1998). As we have previously shown in wild-type mice, the sulindac diet increased HIF1α expression in Hif1αF/F mice, and this effect was most pronounced in the inflammatory colon lesions (Fig. 3A). HIF1α expression remained low in the colon of the Hif1αΔIEC mice that had been treated with sulindac.Fig. 3.

DMM019000F3: Treatment with sulindac upregulates HIF2α and downregulates MIF in Hif1αΔIEC mice compared with Hif1αF/F mice. Q-PCR analysis for gene expression of Hif1α (A), ITF (B), Glut1 (C), Pgk1 (D), Vegfa (E), Hif2α (F), MIF (G) and the macrophage marker F4/80 (H). RNA was extracted from the mucosal scrapings, and lesions were harvested from the proximal colon of Hif1αΔIEC and Hif1αF/F mice that had been treated with sulindac (Sul) or the control (Con) diet. The q-PCR primers for Hif1α span exons 2 and 3. Gene expression was normalised to that of Rpl19. Error bars indicate s.e.m. Star (*) indicates P<0.05.

Mentions:
We observed a 19-fold reduction of Hif1α mRNA expression in Hif1αΔIEC mice compared with that of the control genotype (Fig. 3A). The generation of Hif1αΔIEC involves deletion of exon 2, which contains sequences encoding the basic helix-loop-helix (bHLH) domain that is essential for DNA binding and dimerisation of HIF1α and HIF1β (Jiang et al., 1996), and that results in downregulation of HIF1α-target genes (Iyer et al., 1998; Ryan et al., 1998). As we have previously shown in wild-type mice, the sulindac diet increased HIF1α expression in Hif1αF/F mice, and this effect was most pronounced in the inflammatory colon lesions (Fig. 3A). HIF1α expression remained low in the colon of the Hif1αΔIEC mice that had been treated with sulindac.Fig. 3.